The invention describes a method for forming a three-dimensional (3D) scaffold structure bio-compatible for use as a medical implant and, more specifically, for forming, using a rapid-prototyping method, a 3D scaffold structure that can be implanted in a living body as replacement for bone and for promoting bone growth.
Bone graft is used to fill spaces in bone tissue that are the result of trauma. Clinicians perform bone graft procedures for several reasons, often to fill a bone void created by a loss of bone due to trauma, degeneration due to disease or other loss of tissue. In many instances, the clinician also must rely on the bone graft material to provide some mechanical support, as in the case of subchondral bone replacement or compaction grafting around total joint replacement devices. In these instances, clinicians pack the material into the defect to create a stable platform to support the surrounding tissue and hardware. Additionally, the clinician may rely on the material to facilitate cell growth and extracellular matrix production.
There are several options available to the orthopedic clinician for bone graft material, including autografts (bone from the patient), allografts (cadaver bone), and a variety of artificial or synthetic bone substitute materials. Autografts are comprised of cancellous bone and cortical bone. Cancellous bone grafts provide virtually no structural integrity. Bone strength increases as the graft is incorporated and new bone is laid down. For cortical bone, the graft initially provides some structural strength. However, as the graft is incorporated by the host bone, nonviable bone in the graft is removed by osteoclast resorption, reducing the strength of the graft. The use of autograft bone may result in severe patient pain at the harvest site, and there is, of course, a limit to the amount of such bone that can be harvested from the patient. Allografts are similar to autografts in that they are comprised of cancellous and/or cortical bone with greater quantities and sizes being available. Sterilization techniques for allografts may compromise the structural and biochemical properties of the graft. The use of allograft bone bears at least some risk of transfer of disease and the risk that the graft may not be well incorporated.
Synthetically derived bone graft substitutes have advantages over human derived bone grafts and naturally derived substitutes, including: 1) more control over product consistency; 2) less risk for infection and disease; 3) no morbidity or pain caused by harvesting of the patient's own bone for graft; and 4) availability of the substitute in many different volumes (that is, it is not limited by harvest site of the patient). The bone graft materials that have been used commercially exhibit various levels of bioactivity and various rates of dissolution. These materials are currently available in several forms: powders, gels, slurry/putties, tablets, chips, morsels, and pellets, in addition to shaped products (sheets, and blocks). In many instances, the form of bone graft products is dictated by the material from which they are made. Synthetic materials (such as calcium sulfates or calcium phosphates) have been processed into several shapes (tablets, beads, pellets, sheets, and blocks) and may contain additives such as antibiotics or bioactive agents. Allograft products, in which the source of the bone graft material is a donor, are typically available as chips and can be mixed with a gel to form a composite gel or putty. None of the current bone graft products and technologies is capable of offering an allograft with a scaffold structure, nor does it match the size and shape of the surgical defect. Furthermore, none but one of the current products and technologies offered for bone graft materials is capable of offering an allograft or synthetic granule or shape containing a bioactive agent or agents, such as an antibiotic or bone morphogenetic proteins.
For structural bone repair materials to be conveniently used, they must be capable of being formed into complex shapes that are designed to fit the contours of the repair site. An accurately contoured graft will enhance the integration of natural bone and provide better load carrying capability. Intimate, load carrying contact often is required between the natural bone and the bone substitute material to promote bone ingrowth, remodeling, and regeneration, leading to incorporation of the graft by host bone. Ideally, the strength, stiffness, and resilience (that is, its response to load and rate of load) of the bone substitute material should be similar to that of natural bone. Ideal mechanical properties of any scaffold will vary depending on the clinical application because the elastic modulus of bone differs according to anatomical location.
Many materials have been proposed for use as bone substitute materials, ranging from shaped porous metal objects suitable for defect filling around knee and hip joint replacements on the one hand to shaped ceramic materials on the other. Ceramic materials by and large have been formed through a sintering process in which a powder of a ceramic material such as zirconia is compressed to a desired shape in a mold and is then heated to sintering temperatures. The porosity of the resulting material is commonly quite low unless a porogen is added to the powder before molding. Materials employing calcium phosphates (for example: fluorapatite, hydroxyapatite, and tricalcium phosphate) can also be sintered in this manner; the hydroxyapatite and the tricalcium phosphate having the capacity for acting as a substrate for bone growth (osteoconductivity).
Metal or ceramic materials that have been proposed for bone substitutes have been of low porosity and have involved substantially dense metals and ceramics with semi-porous surfaces filled or coated with a calcium phosphate based material. The resulting structure has a dense metal or ceramic core and a surface which is a composite of the core material and a calcium phosphate, or a surface which is essentially a calcium phosphate. The bone substitute materials of this type commonly are heavy and dense, and often are significantly stiffer in structure than bone. Whereas natural bone, when stressed in compression, fails gradually (some components of the bone serving to distribute the load), bone substitute materials such as those described above commonly fail suddenly and catastrophically.
Porous ceramic materials such as hydroxyapatite and soluble glasses have also been used as scaffolds for the ingrowth of tissue due to compositional and morphological biocompatability. For example, the porosity of such materials promotes cell infiltration. A variety of methods are used to prepare porous ceramic scaffolds (prostheses), such as hydrothermally treating animal bone or coral, burning off polymer beads mixed into a ceramic body, vapor deposition on foam, infiltration of polymer foam with a ceramic slip and foaming a ceramic slip.
One limitation exhibited by porous ceramic materials is their inherent brittleness. Attempts to address this limitation have included back-filling a ceramic foam with monomer solutions of PMMA or PLA, draining excess solution from the ceramic foam then polymerizing through curing and/or drying in order to impart some toughness to the ceramic foam. Others have proposed laminating solid or porous polymeric layers to a ceramic foam structure.
Independent from proposed uses in combination with ceramics, polymeric foams have utility in the repair and regeneration of tissue. For example, amorphous, polymeric foam has been used to fill voids in bone. Various methods have been explored for preparing the polymer foams, using, e.g., leachables; vacuum foaming techniques; precipitated polymer gel masses; and polymer melts with fugitive compounds that sublime at temperatures greater than room temperature. Additionally, some methods allow the incorporation of thermally sensitive compounds like proteins, drugs, and other additives. These materials however lack the structural integrity required for use as scaffolds for some medical applications.
In the case of fracture or other injury to bone, proper bone healing and favorable bone remodeling is highly dependent on maintaining stability between bone fragments and on maintaining physiologic strain levels. External structural support can be gained using external braces, casts and the like. Internal structural support commonly is supplied by internal fixation devices such as bone plates, screws, and intermedullary rods, some of which may need to be surgically removed and all of which may prove to be burdensome and traumatic to a patient.
There is thus a need for a product that is a bone substitute material and that also provides structural support. This is especially so in the replacement or repair of long bones of the lower extremities and for use in spinal fusion techniques. Trauma, osteoporosis, severe osteoarthritis or rheumatoid arthritis, joint replacement, and bone cancers may call for treatment involving the use of structural bone substitute materials. A successful bone graft requires an osteoconductive matrix providing a scaffold for bone ingrowth, osteoinductive factors providing chemical agents that induce bone regeneration and repair, osteogenic cells providing the basic building blocks for bone regeneration by their ability to differentiate into osteoblasts and osteoclasts, and structural integrity provided to the graft site suitable for the loads to be carried by the graft. Tissue regeneration devices must be porous with interconnected pores to allow cell and tissue penetration. Factors such as pore size, shape, and tortuosity can all affect tissue ingrowth. Needed are methods to construct intricate three-dimensional structures from biocompatible materials with controllable pore structure and suitable mechanical strength and fluid transport characteristics.